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3.
Glob Heart ; 15(1): 58, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32923351

RESUMO

Whilst current public health measures focused on good hygiene practices and limiting person-to-person transmission contribute effectively in managing the COVID-19 pandemic, they will not prevent all individuals from becoming infected. Thus, it is of importance to explore what individuals could do to mitigate adverse outcomes. The value of beneficial health behaviours and a healthy lifestyle to improve immune functioning and lower adverse consequences of COVID-19 are increasingly being emphasized. Here we discuss seven key health behaviours and corresponding recommendations that may assist in reducing unfavourable COVID-19 outcomes.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/prevenção & controle , Infecções por Coronavirus/complicações , Comportamentos Relacionados com a Saúde , Estilo de Vida Saudável , Síndrome Metabólica/complicações , Síndrome Metabólica/prevenção & controle , Pneumonia Viral/complicações , Humanos , Pandemias , Guias de Prática Clínica como Assunto
4.
J Am Coll Cardiol ; 76(6): 703-714, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32762905

RESUMO

BACKGROUND: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population. OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians. METHODS: This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India. RESULTS: The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each). CONCLUSIONS: The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.

5.
Eur J Epidemiol ; 35(8): 743-748, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32656618

RESUMO

In low and middle-income countries (LMICs), strict social distancing measures (e.g., nationwide lockdown) in response to the COVID-19 pandemic are unsustainable in the long-term due to knock-on socioeconomic and psychological effects. However, an optimal epidemiology-focused strategy for 'safe-reopening' (i.e., balancing between the economic and health consequences) remain unclear, particularly given the suboptimal disease surveillance and diagnostic infrastructure in these settings. As the lockdown is now being relaxed in many LMICs, in this paper, we have (1) conducted an epidemiology-based "options appraisal" of various available non-pharmacological intervention options that can be employed to safely lift the lockdowns (namely, sustained mitigation, zonal lockdown and rolling lockdown strategies), and (2) propose suitable application, pre-requisites, and inherent limitations for each measure. Among these, a sustained mitigation-only approach (adopted in many high-income countries) may not be feasible in most LMIC settings given the absence of nationwide population surveillance, generalised testing, contact tracing and critical care infrastructure needed to tackle the likely resurgence of infections. By contrast, zonal or local lockdowns may be suitable for some countries where systematic identification of new outbreak clusters in real-time would be feasible. This requires a generalised testing and surveillance structure, and a well-thought out (and executed) zone management plan. Finally, an intermittent, rolling lockdown strategy has recently been suggested by the World Health Organization as a potential strategy to get the epidemic under control in some LMI settings, where generalised mitigation and zonal containment is unfeasible. This strategy, however, needs to be carefully considered for economic costs and necessary supply chain reforms. In conclusion, while we propose three community-based, non-pharmacological options for LMICs, a suitable measure should be context-specific and based on: (1) epidemiological considerations, (2) social and economic costs, (3) existing health systems capabilities and (4) future-proof plans to implement and sustain the strategy.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/prevenção & controle , Máscaras , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Quarentena , Isolamento Social , Betacoronavirus , Coronavirus , Infecções por Coronavirus/epidemiologia , Humanos , Máscaras/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Saúde Pública , Quarentena/estatística & dados numéricos
6.
BMJ ; 370: m2194, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641421

RESUMO

OBJECTIVE: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. DESIGN: Prospective case-cohort study. SETTING: Populations from eight European countries. PARTICIPANTS: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. MAIN OUTCOME MEASURE: Incident type 2 diabetes. RESULTS: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. CONCLUSIONS: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.


Assuntos
Ácido Ascórbico/sangue , Carotenoides/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Frutas , Verduras , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Dieta , Europa (Continente) , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-32668607

RESUMO

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5-30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.


Assuntos
Saúde Pública , Luz Solar , Raios Ultravioleta , Europa (Continente) , Humanos , Queimadura Solar , Vitamina D , Deficiência de Vitamina D
8.
9.
Eur J Epidemiol ; 35(5): 389-399, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32430840

RESUMO

To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs-increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal "break" when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R0) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a "schedule" of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/prevenção & controle , Coronavirus , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Humanos , Modelos Teóricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão
10.
Eur J Epidemiol ; 35(1): 49-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31720912

RESUMO

To inform evidence-based practice in health care, guidelines and policies require accurate identification, collation, and integration of all available evidence in a comprehensive, meaningful, and time-efficient manner. Approaches to evidence synthesis such as carefully conducted systematic reviews and meta-analyses are essential tools to summarize specific topics. Unfortunately, not all systematic reviews are truly systematic, and their quality can vary substantially. Since well-conducted evidence synthesis typically involves a complex set of steps, we believe formulating a cohesive, step-by-step guide on how to conduct a systemic review and meta-analysis is essential. While most of the guidelines on systematic reviews focus on how to report or appraise systematic reviews, they lack guidance on how to synthesize evidence efficiently. To facilitate the design and development of evidence syntheses, we provide a clear and concise, 24-step guide on how to perform a systematic review and meta-analysis of observational studies and clinical trials. We describe each step, illustrate it with concrete examples, and provide relevant references for further guidance. The 24-step guide (1) simplifies the methodology of conducting a systematic review, (2) provides healthcare professionals and researchers with methodologically sound tools for conducting systematic reviews and meta-analyses, and (3) it can enhance the quality of existing evidence synthesis efforts. This guide will help its readers to better understand the complexity of the process, appraise the quality of published systematic reviews, and better comprehend (and use) evidence from medical literature.


Assuntos
Guias como Assunto , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Humanos
11.
Int J Obes (Lond) ; 44(3): 664-674, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31848457

RESUMO

BACKGROUND: While recent evidence suggests that the overall prevalence of overweight in young children in Bangladesh is low, little is known about variation in trends by sex, socioeconomic status, urbanicity, and region. We investigated the trends in overweight among children aged 24-59 months by these factors, using nationally representative samples from Bangladesh Demographic and Health Surveys (BDHS) between 2004 and 2014. METHODS: Data from four BDHS surveys conducted between 2004 and 2014, with valid height and weight measurements of children, were included in this study (n = 15,648). BMI was calculated and the prevalence of overweight (including obesity) was reported using the International Obesity Taskforce (IOTF) classification system. To explore the association between socioeconomic status and childhood overweight, we used multivariable logistic regression. RESULTS: The overall prevalence of overweight among children aged 24-59 months increased from 1.60% (95% CI: 1.20-2.05%) in 2004 to 2.33% (95% CI: 1.82-2.76%) in 2014. Among girls, the overweight trend increased significantly (adjusted odds ratio (OR) comparing 2014 vs. 2004: 2.02 95% CI: 1.52-2.68), whereas among boys the trend remained steady. When compared with households with the poorest wealth index, households with richest wealth index had higher odds of childhood overweight among both boys (OR 2.39, 95% CI: 1.76-3.25) and girls (OR 1.86, 95% CI: 1.35-2.55). Higher household education level was also associated with childhood overweight. Subgroup analyses showed that relative inequalities by these factors increased between 2004 and 2014 when adjusted for potential confounders. CONCLUSIONS: There is a rising trend in overweight prevalence exclusively among girls aged 24-59 months in Bangladesh. Childhood overweight is associated with higher household education and wealth index, and the relative disparity by these factors appears to be increasing over time. These unmet inequalities should be considered while developing national public health programs and strategies.

13.
J Hum Hypertens ; 33(10): 703-715, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31346255

RESUMO

Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to systematically review studies investigating the association between epigenetic marks (global, candidate-gene or genome-wide methylation of DNA, and histone modifications) and blood pressure or hypertension. Five bibliographic databases were searched until the 7th of December 2018. Of 2984 identified references, 26 articles based on 25 unique studies met our inclusion criteria, which involved a total of 28,382 participants. The five studies that assessed global DNA methylation generally found lower methylation levels with higher systolic blood pressure, diastolic blood pressure, and/or presence of hypertension. Eighteen candidate-gene studies reported, in total, 16 differentially methylated genes, including renin-angiotensin-system-related genes (ACE promoter and AGTR1) and genes involved in sodium homeostasis and extracellular fluid volume maintenance system (NET promoter, SCNN1A, and ADD1). Between the three identified epigenome-wide association studies (EWAS), lower methylation levels of SULF1, EHMT2, and SKOR2 were found in hypertensive patients as compared with normotensive subjects, and lower methylation levels of PHGDH, SLC7A11, and TSPAN2 were associated with higher systolic and diastolic blood pressure. In summary, the most convincing evidence has been reported from candidate-gene studies, which show reproducible epigenetic changes in the interconnected renin-angiotensin and inflammatory systems. Our study highlights gaps in the literature on the role of histone modifications in blood pressure and the need to conduct high-quality studies, in particular, hypothesis-generating studies that may help to elucidate new molecular mechanisms.


Assuntos
Pressão Sanguínea/genética , Montagem e Desmontagem da Cromatina , Metilação de DNA , Epigênese Genética , Histonas/metabolismo , Hipertensão/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Fenótipo , Fatores de Risco
14.
Int J Inflam ; 2019: 6273680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205673

RESUMO

Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.

15.
16.
Hum Reprod Update ; 25(2): 257-271, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508190

RESUMO

BACKGROUND: The effect of postmenopausal hormone therapy (HT) on cardiovascular disease (CVD) risk remains controversial. OBJECTIVE AND RATIONALE: We aimed to systematically review the evidence regarding the role of dose, route of hormone administration, timing of initiation and duration of HT on cardiovascular risk among postmenopausal women. SEARCH METHODS: The electronic databases Medline Ovid, Web of Science and Cochrane Central were systematically searched to identify studies published before 30 January 2018. Reference lists, using Elsevier's Scopus, of the included studies were searched for further identification of relevant studies. Clinical trials and observational studies that assessed clinical and subclinical cardiovascular outcomes in relation to dose, route of administration, duration of use, or timing of HT initiation among postmenopausal women were included. Data were extracted by independent reviewers using a pre-designed data collection form. The Cochrane Collaboration's tool and the Newcastle-Ottawa Scale were used by two independent investigators to assess the risk of bias in RCTs and in prospective observational studies, respectively. OUTCOMES: In total, 33 unique studies (6 trials and 27 prospective observational studies) were identified, including a total of 2 588 327 women. The synthesis of the existing knowledge on this topic was challenging due to inconsistent findings between some studies, caused by substantial diversity in scientific rigor and quality across the available literature. Overall, the evidence did not support the concerns that oral or transdermal HT increases heart disease risk. Contrary, observational data showed that a beneficial cardioprotective effect can be observed even with use of low doses of oral HT (effect of 0.3 mg/day of oral conjugated equine estrogen was similar to that seen with the standard dose of 0.625 mg/day), but clinical trials to support a cardioprotective benefit of HT in primary prevention have not been identified. Furthermore, the current data suggested that oral and transdermal HT, in dose-dependent manner and irrespective of HT formulation, may increase thromboembolic risk, as well as risk of stroke. However, transdermal estrogen with <50 µg/day of estrogen combined with micronized progesterone appears to be the safer choice with respect to thrombotic and stroke risk. Also, vaginal HT administration may play a role in myocardial infarction and stroke risk prevention, but this is based on limited evidence and requires further investigation. The timing of HT initiation and duration may be important factors to consider when prescribing HT especially in women with adverse cardiometabolic profile and pre-existing conditions such as coronary/carotid atherosclerosis, which are at risk of developing, and thus progressing to CVD. The quality of evidence was generally low or moderate and the findings were based mostly on observational data. WIDER IMPLICATIONS: Use of low-dose oral and transdermal HT appears to be safe with regard to CVD risk in women in menopausal transition and within the first years (e.g. 10 years) after menopause onset. In women with increased baseline thromboembolic risk, alternative non-hormonal medications are suggested as first-line treatment and transdermal estradiol alone or with micronized progesterone only should be considered when these options are not effective. When HT is initiated >10 years since the menopause onset (>60 years old), due to greater absolute risks of coronary heart disease, stroke and venous thromboembolism, HT should be used for the shortest time possible and in lowest possible dose and preferably transdermal administration should be recommended. However, an individualized treatment approach including baseline CVD risk assessment should be applied when prescribing HT. The majority of studies included in the current review are from North American and European populations, which might limit the generalizability of the findings of this review to the other populations. Finally, the quality of evidence included in this review was generally low or moderate, highlighting a need for more rigorous research to help us better understand HT and cardiovascular health.


Assuntos
Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios/efeitos adversos , Terapia de Reposição de Estrogênios/métodos , Estrogênios/uso terapêutico , Progesterona/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Estradiol/efeitos adversos , Estrogênios/efeitos adversos , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Pós-Menopausa , Progesterona/efeitos adversos , Estudos Prospectivos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Tromboembolia Venosa/induzido quimicamente
17.
Adv Nutr ; 9(6): 726-740, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462180

RESUMO

Phytoestrogens might have advantageous effects on diabetes in women. We performed a systematic review and meta-analysis to determine the effect of phytoestrogens on glucose homeostasis and the risk of type 2 diabetes (T2D) among women. Randomized controlled trials (RCTs) and prospective observational studies that assessed associations of phytoestrogens (supplementation, dietary intake, or biomarkers) with fasting glucose or insulin, homeostatic model assessment of insulin resistance (HOMA-IR), or with the risk of T2D were included. We identified 18 RCTs (n = 1687 individuals) investigating the effect of phytoestrogen supplementation on glucose homeostasis and 9 prospective population-based studies (n = 212,796 individuals) examining the association between phytoestrogen intake and the risk of T2D. Compared with placebo, phytoestrogen supplementation resulted in improvements in fasting glucose and HOMA-IR: the pooled mean differences of changes were -0.12 mmol/L (95% CI: -0.20, -0.03 mmol/L) and -0.24 mmol/L (95% CI: -0.45, -0.03 mmol/L), respectively. Although there was no significant decrease in insulin concentrations with overall phytoestrogen supplementation, the pooled mean difference in changes was -0.99 pmol/L (95% CI: -4.65, 2.68 pmol/L). However, the results of RCTs varied by type of phytoestrogens: soy-derived isoflavones and genistein improved glucose homeostasis, whereas isoflavone mix and daidzein had no effect or were associated with an adverse glycemic profile. Higher dietary phytoestrogen intake was associated with a 10% lower risk of developing T2D in observational studies (pooled RR: 0.90; 95% CI: 0.85, 0.96; for the highest compared with the lowest quantiles). Results were similar when the analyses were restricted to only medium- and high-quality studies. Overall, phytoestrogens may have a positive influence on glycemia and could be used for diabetes prevention in women. However, for some individual types of phytoestrogens, such as mixed isoflavones, caution is needed in recommending their use in women, because their use could lead to an adverse glycemic profile in women.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Homeostase/efeitos dos fármacos , Fitoestrógenos/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/etiologia , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
18.
Nat Genet ; 50(11): 1514-1523, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30275531

RESUMO

The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).


Assuntos
Grupos Étnicos/genética , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Veteranos/estatística & dados numéricos , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Grupos Étnicos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/genética , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Hispano-Americanos/genética , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
19.
BMJ ; 362: k3310, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158148

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis of epidemiological studies investigating the association of arsenic, lead, cadmium, mercury, and copper with cardiovascular disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, and Web of Science searched up to December 2017. REVIEW METHODS: Studies reporting risk estimates for total cardiovascular disease, coronary heart disease, and stroke for levels of arsenic, lead, cadmium, mercury, or copper were included. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks were standardised to a common scale and pooled across studies for each marker using random effects meta-analyses. RESULTS: The review identified 37 unique studies comprising 348 259 non-overlapping participants, with 13 033 coronary heart disease, 4205 stroke, and 15 274 cardiovascular disease outcomes in aggregate. Comparing top versus bottom thirds of baseline levels, pooled relative risks for arsenic and lead were 1.30 (95% confidence interval 1.04 to 1.63) and 1.43 (1.16 to 1.76) for cardiovascular disease, 1.23 (1.04 to 1.45) and 1.85 (1.27 to 2.69) for coronary heart disease, and 1.15 (0.92 to 1.43) and 1.63 (1.14 to 2.34) for stroke. Relative risks for cadmium and copper were 1.33 (1.09 to 1.64) and 1.81 (1.05 to 3.11) for cardiovascular disease, 1.29 (0.98 to 1.71) and 2.22 (1.31 to 3.74) for coronary heart disease, and 1.72 (1.29 to 2.28) and 1.29 (0.77 to 2.17) for stroke. Mercury had no distinctive association with cardiovascular outcomes. There was a linear dose-response relation for arsenic, lead, and cadmium with cardiovascular disease outcomes. CONCLUSION: Exposure to arsenic, lead, cadmium, and copper is associated with an increased risk of cardiovascular disease and coronary heart disease. Mercury is not associated with cardiovascular risk. These findings reinforce the importance of environmental toxic metals in cardiovascular risk, beyond the roles of conventional behavioural risk factors.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Poluentes Ambientais/toxicidade , Poluição Ambiental/efeitos adversos , Metais Pesados/toxicidade , Humanos , Medição de Risco , Fatores de Risco
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